The overall objective of the Solid Tumor Autologous Marrow Program (STAMP) is to integrate basic and clinical research with the goal of exploiting intensive combination chemotherapy particularly with alkylating agents. The clinical trials are designed with curative intent for patients with metastatic breast cancer, lymphoma, small cell lung cancer, and testicular cancer. Dose escalation is made possible by advances in supportive care particularly autologous marrow transplantation, the acquisition of marrow stem cells from the peripheral blood, and the use of hematopoietins. To optimize this clinical approach, we have a major parallel laboratory efforts. We have extensive ongoing pre-clinical modeling studies for STAMP including studies of the biology and biochemistry of alkylating agents with relation to dose, schedule, resistance, cross resistance, combinations, and modulators. Our clinical trials have been, and will continue to be profoundly influenced by these laboratory studies. The use of alkylating agent modulators is prominently featured in this Grant. Modulators of determinants of sensitivity and resistance to alkylating agents have been defined and are the subject of pre-clinical, and clinical studies as well as selected biochemical studies emphasizing topoisomerases. To define new and clinically relevant targets for alkylating agents, we have under study the activation of early response genes by alkylating agents. These involve a cascade with resultant repair of the potential lethal damage or cell death and provide potential targets for alkylating agents and particularly for modulators thereof. Finally, we recognize the need for tight quantitative, sharply-focused experimental designs. To this extent, all of our studies proceed from the planning stage with our biostatisticians who are also responsible at the data management, collection, analysis and interpretation levels.